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Journal of Lipid Research, Vol. 44, 994-1000, May 2003
Copyright © 2003 by Lipid Research, Inc.

Characterization of the long pentraxin PTX3 as a TNF-induced secreted protein of adipose cells

Anissa Abderrahim-Ferkoune^1,*, Olivier Bezy^1,*, Chiara Chiellini, Margherita Maffei, Paul Grimaldi, Frédéric Bonino^*, Naïma Moustaid-Moussa^**, Fabio Pasqualini, Alberto Mantovani, Gérard Ailhaud^* and Ez-Zoubir Amri^2,*

^* Institute of Signaling, Developmental Biology and Cancer Research, Centre de Biochimie, UMR 6543 CNRS, Faculté des Sciences, Parc Valrose, 06108 Nice cedex 2, France
INSERM U470, Faculté des Sciences, Parc Valrose, 06108 Nice cedex 2, France
Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy
^** Department of Nutrition, University of Tennessee, Knoxville, TN 37939
Department of Immunology and Cell Biology, Mario Negri Institute for Pharmacology Research, Via Eritrea 62, Milano, Italy

² To whom correspondence should be addressed. e-mail: amri{at}unice.fr

Exposure of preadipocytes to long-chain fatty acids induces the expression of several markers of adipocyte differentiation. In an attempt to identify novel genes and proteins that are regulated by fatty acids in preadipocytes, we performed a substractive hybridization screening and identified PTX3, a protein of the pentraxin family. PTX3 mRNA expression is transient during adipocyte differentiation of clonal cell lines and is absent in fully differentiated cells. Stable overexpression of PTX3 in preadipocytes has no effect on adipocyte differentiation. In line with this, PTX3 mRNA is expressed in the stromal-vascular fraction of adipose tissue, but not in the adipocyte fraction; however, in 3T3-F442A adipocytes, the PTX3 gene can be reinduced by tumor necrosis factor (TNF) in a dose-dependent manner. This effect is accompanied by PTX3 protein secretion from both 3T3-F442A adipocytes and explants of mouse adipose tissue. PTX3 mRNA levels are found to be higher in adipose tissue of genetically obese mice versus control mice, consistent with their increased TNF levels.

In conclusion, PTX3 appears as a TNF-induced protein that provides a new link between chronic low-level inflammatory state and obesity.

Abbreviations: LIF, leukemia inhibitory factor; PPAR, peroxisome proliferator-activated receptor ; TNF, tumor necrosis factor

Supplementary key words tumor necrosis factor • cytokines • adipocytes

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